Corneal transplant surgery is required for the surgical treatment of endothelial diseases of the cornea including glaucoma, edema and Fuchs endothelial dystrophy.
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. The cornea, with the anterior chamber and lens, refracts light and accounts for approximately two-thirds of the eye's total optical power.
In humans, the refractive power of the cornea is approximately 43 diopters. While the cornea contributes most of the eye's focusing power, its focus is fixed. The curvature of the lens, on the other hand is adjusted by the eye muscles to “tune” the focal length of the eye, to bring objects at different distances into focus.
Because transparency is of prime importance, the cornea does not have blood vessels and no direct blood supply. It receives oxygen that first dissolves in the tears and then diffuses throughout the cornea to keep it healthy. It receives nutrients via diffusion from the tear fluid through the outside surface, from the aqueous humour through the inside surface, and also from neurotrophins supplied by nerve fibres that innervate it. In humans, the cornea has a diameter of about 11.5 mm and a thickness of 0.5-0.6 mm in the center, which drops off to about 0.6-0.8 mm at the periphery.
In humans (and other higher vertebrates) the cornea is fused with the skin to form a single multiple layers structure.
The human cornea, like those of other primates, has five layers. From the anterior to posterior the five layers of the human cornea area                (i) Conical epithelium—this is an exceedingly thin multicellular epithelial tissue layer (non-keratinized stratified squamous epithelium) of fast-growing and easily regenerated cells that is kept moist with tears. Irregularity or edema of the corneal epithelium disrupts the smoothness of the air-tear film interface which is the most significant component of the total refractive power of the eye, thereby reducing visual acuity. The Conical epithelium is continuous with the conjunctival epithelium, and consists of about 6 layers of cells which are shed constantly on the exposed layer and are regenerated by multiplication in the basal layer.        (ii) Bowman's layer (also erroneously known as the anterior limiting membrane). This is a tough layer that protects the corneal stroma. It consists of similar irregularly arranged collagen fibers that are mainly type I collagen fibrils. These fibrils interact with and attach on to each other. The bowman's layer is 8 μm-14 μm thick.        (iii) Conical stroma (also known as the substantia propria). This is a thick, transparent middle layer consisting of regularly arranged collagen fibers along with sparsely distributed interconnected keratocytes, which are the cells for general repair and maintenance.—The keratocytes are parallel and are superimposed, in a manner analogous to book pages. The corneal stroma consists of approximately 200 layers of mainly type I collagen fibrils. Each layer is 1.5 μm-2.5 μm. The stroma is responsible for up to 90% of the corneal thickness.        (iv) Descemet's membrane (also known as the posterior limiting membrane) is a thin cellular layer that serves as the modified basement membrane of the corneal endothelium, from which the cells are derived. This layer is composed mainly of collagen type IV fibrils which are less rigid than collagen type I fibrils, and are around 5 μm-20 μm thick, depending on the subject's age.        (v) Conical endothelium: a simple squamous or low cuboidal monolayer, approx 5 μm thick, of mitochondria-rich cells. These cells are responsible for regulating fluid and solute transport between the aqueous and corneal stromal compartments. The corneal endothelium is bathed with aqueous humor. Unlike the conical epithelium the cells of the endothelium do not regenerate. Instead, they stretch to compensate for dead cells which reduce the overall cell density of the endothelium and have an impact on fluid regulation. If the endothelium can no longer maintain a proper fluid balance, stromal swelling due to excess fluids and subsequent loss of transparency will occur and this may cause corneal edema and interference with the transparency of the cornea and thus impairing the image formed.        
The cornea is a protective domed layer of clear tissue covering the front of the eye. The endothelial cells are non-replicating. In normal healthy membranes there is a cell density of between about 1500 and 2500 cells per mm2.
Once the population of endothelial cells decreased below a critical number that is about 600 per mm2, the cornea becomes edematous while losing its optical quality. This condition is known as corneal edema.
In corneal edema, the cornea becomes overly hydrated by accumulated fluid. Corneal edema may result in deteriorated vision. If corneal edema becomes severe, blisters on the cornea can appear. In rare cases, surgery may be needed to treat conical edema. In one technique, the cornea is replaced with a transplanted cornea.
Corneal edema is a result of a lack of viable cells in the corneal endothelium. The purpose of a surgical transplant is to replace a section of the corneal endothelium lacking healthy cells, with a section of donor endothelium having healthy cells. The complete replacement of the damaged cornea has been the treatment for corneal edema for many years. However, this approach has some disadvantages, including a high degree of post-operative astigmatism, a lack of predictable refractive outcome, and disturbance to the ocular surface.
Recently, the surgical trend has shifted towards removal of only a thin layer of tissue from a diseased eye and replacing it with corresponding donor tissue from a fresh human cadaver eye. The implanted tissue consists of the posterior corneal stroma, a thin layer of connective tissue known as Descemet's membrane that carries on its surface a monolayer of the endothelial cells. These cells actively “pump” the fluids from the cornea and maintain its clarity
One surgical technique for replacing the Descemet's membrane is known as DSEK, which is an acronym for Descemet Stripping Endothelial Keratoplasty. DSEK is performed through a relatively small corneal incision compared to that required for standard perforating keratoplasty, thereby avoiding ‘open sky’ surgery with its risk of hemorrhage or expulsion, decreasing the incidence of postoperative wound dehiscence, and reducing unpredictable refractive outcomes. DSEK has dramatically changed the treatment of corneal endothelial disease.
It is believed that DSEK and similar techniques also decrease the rate of transplant rejection. However, it will be appreciated that where the implanted tissue consists of a Descemet membrane with the endothelial cells on one side and a thin layer of stroma on the other side, the implanted tissue is very fragile. When the cornea is processed pre-operatively and later during surgical implantation in the recipient eye, endothelial cell damage may be massive, and it has been estimated that on average some 30%-40% of the cells die in the first year. This is the main cause of DSEK transplant failure.
Handling Descemet's membrane is required on two occasions. Firstly when the tissue is obtained from the donor cornea and secondly when the donor tissue is manipulated into the required position on the recipient's cornea. During both removal from the cadaver and positioning in the patient's eye, Descemet's membrane requires manipulation and positioning, typically with surgical blades, hooks and the like. These manipulations may cause damage to some or all of the endothelial cells, resulting in immediate post-operative reduction in cell number with an accumulating cell number decrease over the first year due to the death of partially damaged cells. This diminishes the likelihood of a long term successful surgical outcome.
Eye banks have been providing full thickness corneas for surgical transplantation for many years. However, with the trend towards replacement of a thin membrane only, by Descemet's stripping automated endothelial keratoplasty, (DSAEK) and to minimize the damage thereto, the donor membrane has been removed from the donor eye with the recipient patient in theatre, and the donor membrane is then immediately inserted into the patient's eye behind the cornea.
Since about 2006, eye banks have developed methodologies for precutting the center of the donor corneal tissue at the eye bank for subsequent use in surgery. For most corneal surgeons, the availability of such precut corneal tissue saves time and money, and reduces the stress of performing the donor corneal dissection in the operating room.
In surgery, a circumferential incision is made in the side of the patient's cornea. A tool is used to cut through Descemet's membrane and to detach it by upwards scraping a section that may be marked by ink on the outside surface of the cornea. The detached section is then removed through the incision. The replacement membrane from the donor is trephined out of the precut area of the donor cornea and the round thin graft is inserted through the incision in the patient's cornea and it is then manipulated into position and floated up into the scraped area by releasing an air bubble under the replacement membrane. This bubble is subsequently absorbed into the eye fluid and disappears.
Successful endothelial implantation procedures provide excellent visual outcomes due to the minimal change in corneal surface topography or refraction. They can successfully treat corneal dysfunction associated with Fuchs' endothelial dystrophy, bullous keratopathy, iridocorneal endothelial syndrome or a failed penetrating graft.
To minimize the damage to the corneal optical quality, the corneal incision is preferably as short as possible. Consequently, the diseased descemet's membrane must be folded to remove it through the short incision. The replacement Descemet's membrane must also be folded to introduce it through the incision. It will be appreciated however, that the manipulation of the donor Descemet's membrane into the patient's eye via a short incision, that is typically about 6 mm on average, with minimal damage to the endothelial cells, is a highly skilled task, requiring highly skilled eye surgeons, making the surgical procedure expensive.
In an earlier application having one common co-inventor, Israel Patent Application IL 222183, filed on 27 Sep. 2012, and then as PCT application number PCT/IL2013/050773, a dedicated apparatus and associated method for sectioning the Descemet's membrane, storing it and for manipulating it for insertion into the eye was described. The device described included a foldable base ring and cover ring that lock together with pins. It also featured a handle that extended across the diameter of the rings, under the membrane, along where the membrane was designed to fold. This promising technique has several disadvantages. Aligning the pins and holes of the two rings has been found to be rather fiddly when working manually. The handle extending across the ring has been found to risk contacting the Descemet membrane to be transplanted and to risk damaging it.
Aspects of the present invention address these issues.